Understanding the chemical structure of an Active Pharmaceutical Ingredient (API) can help predict its stability and potential degradation pathways. This is essential for developing a robust and stable formulation.
Here are some key considerations with examples to illustrate:
1. Hydrolysis-Prone Functional Groups
APIs containing esters, amides, lactones, lactams, and carbamates are prone to hydrolysis in the presence of moisture, which can be catalyzed by acidic or basic conditions.
Example: In antibiotics like penicillin (a β-lactam), the lactam ring is highly susceptible to hydrolysis, particularly in acidic environments.
2. Oxidation Potential
APIs with alcohols, phenols, aldehydes, ethers, amines, and unsaturated bonds are vulnerable to oxidation.
Example: Phenols, like Morphine contains a phenolic hydroxyl group, making it susceptible to oxidative degradation, especially when exposed to air, light, or high temperatures
3. Photolysis (Light Sensitivity)
APIs containing conjugated double bonds, aromatic rings, and carbonyl groups are susceptible to photodegradation.
Example: Nifedipine, a calcium channel blocker, contains conjugated double bonds and aromatic rings, making it light-sensitive.
4. pH-Sensitive Functional Groups
APIs with amines, carboxylic acids, or hydroxyl groups are often sensitive to changes in pH.
Example: Pantoprazole sodium, a proton pump inhibitor, is unstable in acidic environments, which is why it is formulated with an enteric coating to protect it from gastric acid and allow it to reach the intestine for absorption.
5. Decarboxylation
APIs with carboxyl groups (-COOH) may undergo decarboxylation, particularly at elevated temperatures.
Example: Ascorbic acid (Vitamin C) is known to degrade through decarboxylation when exposed to heat, which is why its formulations often include stabilizers and require controlled storage conditions.
6. Reactivity with Impurities
Certain APIs, such as those containing aldehydes or alkenes, can react with impurities or excipients, accelerating degradation.
Example: Aldehyde-containing APIs, like those found in some antibiotic formulations, can react with excipients like sugars, leading to Maillard reactions, which can produce brown-colored by-products and reduce efficacy.
7. Salt Form Stability
APIs formulated as salts (e.g., hydrochloride or sulfate salts) often have different stability profiles compared to their free acid/base forms.
Example: Pantoprazole sodium is more stable as a sodium salt than in its free acid form. The salt form enhances its solubility and bioavailability, but also requires careful protection from moisture and light.
Read also:
- Role of API pH in Formulation Development
- Understanding the Properties of Drug Substance During Literature Search
